Candida albicans is a yeast-like dimorphic fungus that colonises human mucosal surfaces of the mouth, vagina and the gastrointestinal tract as part of the normal microbial flora. It is also an opportunistic pathogen which may trigger a local mucositis such as stomatitis and vaginitis, or it may invade to become a systemic infection.
It is clear that the various outcomes reflect different balances of a host-parasite relationship. While mechanisms of protection are not entirely understood, cellular mechanisms (in particular the T lymphocyte-macrophage unit) are thought to be important in containing both local and systemic spread of the microbe.
The clinical spectrum of mucositis includes:
Recurrent/Persistent Stomatitis.
This is a common problem in the elderly, particularly those with dental prosthesis (dentures). In the latter, about two thirds develop mucositis in relationship to colonisation with C. albicans within the plaque that accumulates on the prosthesis. It is of interest that this situation represents low antigen load and possibly involves a particular host response. Similar fungal problems can be seen in younger subjects, usually wearing prostheses. In subjects with cellular immune deficiency (especially those with HIV disease) persistent C. albicans-related stomatitis (or oral thrush) is a common and significant complication. Subjects using inhaled steroids (usually for asthma) commonly develop oral thrush due to a downregulation of mucosal defence by the steroid.
Recurrent Vulvovaginal Candidiasis.
This is a common problem in women (3-5%) occurring at the time of the menstrual cycle of oestrogen withdrawal (pre-menstrual) when the “mucosal gate” closes, excluding transport of specific T cells into the mucosal tissues. In this group the “T cell pool” is reduced, thus the tenuous hold on restricting C. albicans within the reproductive tract is challenged during this time, with clinical mucositis the result.
Oesophagitis.
This is a common and concerning complication of subjects with impaired immunity, most usually linked to systemic disease such as cancer or in those taking immune suppressive therapy. It is often asymptomatic, following oral thrush, becoming the focus from which life-threatening systemic spread originates. Thus an oral vaccine capable of maximising efficiency of mucosal T cell function, and thus reducing risk of local/systemic disease would be of considerable value for prevention (in ‘at risk’ populations) or therapy (of clinical mucositis) of C. albicans infection of the upper gastrointestinal tract, particularly in immune suppressed subjects would be a primary indication for this vaccine.
Bowel Colonisation.
It is thought that colonisation of the gut with C. albicans triggers an extraordinary range of illnesses and symptoms, from chronic fatigue to “total body allerg”. An industry has grown up around “controlling the Candida”. It would be advantageous to have a vaccine which could reduce the Candida load within the gut by several logs, and thus be an attractive therapeutic proposition.
Other Mucosal Sites and Situations.
The bronchus can become colonised with C. albicans when damaged, especially following repeated antibiotic administration or with mucosal damage. Occasional subjects develop colonisation of the lower urinary tract. A more common problem is recurrent or persistent “thrush” at one or other site following repeated antibiotic use. Such circumstances provide a clinical opportunity for a vaccine, especially in a preventative fashion, ie where certain antibiotics are used long term, the risk of C. albicans overgrowh would be reduced by giving a vaccine.
Therefore, improved vaccines and methods for the prophylactic and/or therapeutic treatment of candidiasis are needed.
An object of the present invention is to overcome or ameliorate at least some of the disadvantages of the prior art treatments, or to provide a useful alternative.